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Mushtaq is medical director at Brooklyn Clinical Research. 

Ammara Mushtaq, MD, discusses the underrepresentation of different races during the pandemic, but also the newer efforts to include and represent these communities in smaller, local studies. 

Correcting the Lack of Diversity in Clinical Trials With Community-Based Studies

Along with a 1 reported case in Massachusetts, the

New Hampshire Department of Health and Human Services (DHHS) has confirmed a person infected with eastern equine encephalitis (EEE) has died. The public health agency said the person was hospitalized due to severe central nervous system disease. The last reported human EEEV infection in New Hampshire was in 2014, when DHHS identified 3 human infections, including 2 fatalities. In the same statement, DHHS mentions there has been 1 confirmed case in Vermont this summer.

On August 16, the Massachusetts Department of Public Health (MDPH) released a statement discussing the confirmation of the first human case of EEE in the state this year. The confirmed case was discovered in an 80 year old man who was exposed to the vector borne disease in Worcester County. As a result, the risk level in the local communities of Douglas, Oxford, Sutton, and Webster has been raised to critical, and in Dudley, Northbridge, and Uxbridge the risk is increased to high.

Additionally, the neighboring communities of Auburn, Charlton, Grafton, Leicester, Mendon, Millbury, Millville, Southbridge, and Upton are now considered at moderate risk according to MDPH.

“This is the first time we have seen a person infected with EEE in Massachusetts since 2020,” Public Health Commissioner Robbie Goldstein, MD, PhD, said in a statement. “EEE is a rare but serious disease and a public health concern. We want to remind residents of the need to protect themselves from mosquito bites, especially in areas of the state where we are seeing EEE activity.

Though very rare, EEE is serious and a potentially fatal disease that can affect people of all ages. EEE is generally spread to humans through the bite of an infected mosquito. There were 12 human cases of EEE in Massachusetts in 2019 with 6 deaths, and 5 human cases with 1 death in 2020. There were no human cases of EEE in Massachusetts in 2021, 2022, or 2023.

EEE has a fatality rate of 33% to 70%, with most deaths occurring 2–10 days after the onset of symptoms.

In addition to a high mortality rate, long-term physical and mental complications, including permanent neurological deficits have been identified in many people who survive EEE.

Plymouth is approximately 40 miles south of Boston along the coast, and Worcester County is in the middle of the state, so the 2 areas are not in close proximity, but due to the elevated risk locally, the town of Plymouth decided to take action in response to outdoor parks. As of last Friday, all town public parks and fields are close daily from dusk until dawn.

“As Mass DPH has now elevated Plymouth’s EEE risk status to high, it is important to take extra precautions when outdoors and follow state and local health guidelines to avoid unnecessary risk to exposure to EEE. The health and safety of our community, residents, and visitors remain our priority,” Plymouth’s Commissioner of Health and Human Services, Michelle Bratti, said in a statement.

According to the Centers for Disease Control and Prevention (CDC) most people who are infected with the virus do not develop symptoms; however, for those that do, the date from the bite to the onset of the illness is 4 to 10 days. EEE can also result in fever or neurologic disease. The type of illness will depend on the age of the person and other factors. Those who are infected can develop meningitis.

There are no FDA-approved treatments for EEE and for patients who develop severe cases, they can be hospitalized to receive supportive treatment.

Over the weekend, MDPH detailed plans of spraying for mosquitos including aerially in areas of Plymouth County, and truck-mounted spraying in parts of Worcester County. As of Saturday, 10 communities in Massachusetts were raised to high or critical risk for EEE virus.

“The risk from EEE is high in parts of Plymouth County and critical in parts of Worcester County,” State Epidemiologist Catherine M. Brown, DVM, said in a statement. “In addition to recommending that people use mosquito repellent with an EPA-registered active ingredient and clothing to reduce exposed skin, we also recommend that evening outdoor events be rescheduled to avoid the hours between dusk and dawn. The mosquitoes most likely to spread EEE are most active during the dusk to dawn hours.”

There are preventative strategies to avoid EEE, and the MDPH has listed such measures 

For those who live in Massachusetts and want more information on EEE, it can be found 

 or by calling the DPH Division of Epidemiology at 617-983-6800.

1.NH DHHS Identifies Person Infected with Eastern Equine Encephalitis Virus in New Hampshire.The New Hampshire Department of Health and Human Services. August 27, 2024. Accessed August 28, 2024.
https://www.dhhs.nh.gov/news-and-media/nh-dhhs-identifies-person-infected-eastern-equine-encephalitis-virus-new-hampshire
2. State health officials announce season’s first human case of Eastern Equine Encephalitis in Massachusetts. MDPH. August 16, 2024. Accessed August 27, 2024.
https://www.mass.gov/news/state-health-officials-announce-seasons-first-human-case-of-eastern-equine-encephalitis-in-massachusetts
3.Plymouth to Close all Public Parks and Fields from Dusk to Dawn. Town of Plymouth. August 23, 2024. Accessed August 27, 2024. PDF.
4. Eastern Equine Encephalitis: Symptoms, Diagnosis, and Treatment. CDC. May 15, 2024. Accessed August 27, 2024.
https://www.cdc.gov/eastern-equine-encephalitis/symptoms-diagnosis-treatment/index.html
5. State officials announce plans to spray for mosquitoes in sections of Worcester and Plymouth counties due to EEE. MDPH. August 24, 2024. Accessed August 27, 2024. 
https://www.mass.gov/news/state-officials-announce-plans-to-spray-for-mosquitoes-in-sections-of-worcester-and-plymouth-counties-due-to-eee



The town of Plymouth decided to prohibit people from using the parks from dusk to dawn due to concerns over eastern equine encephalitis after a man contracted the rare disease in the state.

Concerns Over Mosquito-Borne Illness Causes Massachusetts Town to Create Curfew for Parks, Spraying in Counties

A large randomized controlled trial has found that 7 days of antibiotic treatment for bloodstream infections is noninferior to the standard 14-day regimen. The BALANCE trial, published in 

, involved 3,608 hospitalized patients across 74 hospitals in seven countries. By 90 days, 14.5% of patients in the 7-day group had died, compared to 16.1% in the 14-day group , a difference of 1.6 percentage points (95.7% CI, −4 to 0.8). These findings suggest that shorter antibiotic courses may be a viable option for many patients, especially those who are critically ill.

The trial included a diverse range of hospitalized patients with bloodstream infections, 75.4% of which were community-acquired, and 42.2% originated from the urinary tract. Over half (55%) of participants were critically ill and in the ICU. The trial also showed consistent results across secondary outcomes, including rates of 

 infections and antibiotic-resistant bacterial colonization. Importantly, the trial excluded severely immunosuppressed patients and those with 

 infections, which generally require longer treatment.

In an exclusive interview with Nick Daneman, MD, FRCPC, MSc, one of The BALANCE trials lead investigators, he explained the trial's exclusion criteria. “We included most immunosuppressed patients, and only excluded patients with neutropenia and transplantation.” He continued, “

has many surface molecules that enable it to bind to a range of tissues including bones, joints, and heart valves among others, and so it commonly causes metastatic infection. Therefore, it theoretically requires a longer duration of treatment. Observational studies suggest higher failure rates with shortened treatment. A randomized clinical trial is needed to evaluate Staphylococcus aureus treatment duration but the treatment arms would likely be longer than 7 days in such a trial.”

The shorter 7-day regimen offers both patient-level and public health benefits. Reducing antibiotic exposure could help curb antimicrobial resistance, while potentially lowering healthcare costs by avoiding prolonged treatment. Despite concerns about long-term resistance risks, Daneman pointed out that, “Our primary outcome (death at 90 days) is patient important and is a relatively long-term outcome from the onset of infection. We found a strong signal of non-inferiority of shorter duration treatment. In fact, the point estimate for 90-day death rate was lower in those receiving 7-day treatment. Therefore, we do not have concerns that shorter duration treatment could result in worse outcomes.”

Regarding antimicrobial resistance, Daneman stated, “There are strong theoretical reasons why shorter duration treatment should cause less ecologic harms of antimicrobial resistance than longer duration treatment. Even though we were unable to demonstrate a reduction in resistance with shorter treatment in this study, we think it is very unlikely that resistance would be higher with reduced durations.”

Despite some non-adherence in the trial, with 23.1% of patients in the 7-day group and 10.7% in the 14-day group receiving longer treatment, Daneman provided guidance on safely implementing a 7-day regimen in practice, especially for critically ill patients. He explained, “Our results clearly indicate that a strategy of planning for 7 days of treatment is non-inferior to a strategy of committing all patients to 14 days of treatment. Some patients might require prolongation of treatment beyond 7 days, and that will require clinical judgement. However, randomization to a 7-day strategy was clearly non-inferior to a 14-day strategy even in critically ill patients enrolled in intensive care units.”

These findings align with the CDC’s focus on preventing healthcare-associated infections and minimizing unnecessary antibiotic use. As highlighted in the CDC’s 2023 National and State HAI Progress Report, healthcare-associated infections, particularly those caused by resistant bacteria like MRSA and 

, continue to pose significant challenges.

 Reducing unnecessary antibiotic use, as suggested by the BALANCE trial, could help mitigate the spread of resistant infections and improve patient outcomes.

In conclusion, the BALANCE trial suggests that 7-day antibiotic courses may be a viable alternative to the standard 14-day treatment for bloodstream infections, offering benefits in patient outcomes and reducing unnecessary antibiotic use. These findings support broader efforts to reduce antimicrobial resistance and improve infection prevention practices in healthcare.

1. Antibiotic Treatment for 7 versus 14 Days in Patients with Bloodstream Infections. Published November 20, 2024. Accessed November 21, 2024. 

https://www.nejm.org/doi/full/10.1056/NEJMoa2404991

2. CDC. Current HAI Progress Report. November 7, 2024. Accessed November 21, 2024. 

https://www.cdc.gov/healthcare-associated-infections/php/data/progress-report.html

The BALANCE trial suggests that shorter treatment durations may reduce healthcare costs, antibiotic exposure, and antimicrobial resistance risk, providing an alternative for critically ill patients.

7-Day Antibiotic Regimen Found Noninferior to 14-Day Treatment for Bloodstream Infections

 Paul Feuerstadt, MD, FACG, AGAF, discusses what the data says as well as offers insights about what patients can expect and medical peer-to-peer information about the procedure. 

Two Years FDA Approved, Rebyota Continues to Show Efficacy and Safety

It has been 2 years this month since fecal microbiota, live – jslm (Rebyota) was FDA approved for the indication of recurrent 

 treatment in individuals 18 years of age and older, following antibiotic treatment for recurrent 

New data was released at this year’s ID Week showing its continued efficacy and safety 2 years after the approval. Ferring Pharmaceuticals announced results of its outpatient real-world study using Rebyota. 

In one of the analysis, investigators reviewed the medical records of 64 adult patients from 32 physician offices nationally who received Rebyota from February 2023 to March 2024. In total, 59 patients completed the 8-week follow-up period, of which 75% (n=44) had no CDI recurrence. There were no adverse events reported with treatment aside from minor leakage during administration in 4 patients (6.2%).

Participants in the analysis had a median age of 75 years and were predominantly female (65.6%). Patients had multiple comorbidities (Charlson score 4.5) and 59.4% had 2 or more rCDI risk factors, the most common being age, 65 years or older (75%), and concurrent use of gastric acid suppressants (59.4%). The median number of prior CDI episodes was 3. Fidaxomicin (57.8%) was the most utilized standard-of-care antibiotic for treatment of CDI prior to Rebyota administration.

Additionally there has been other data being released from the PUNCH CD3 trial.

“The open label study data that was published earlier in 2024, which was the largest study that looked at live biotherapeutic products, looked at 697 total patients, so a massive group expanding upon the PUNCH CD3 trial—the randomized control trial that had a placebo arm within this open label study,” said Paul Feuerstadt, MD, FACG, AGAF an associate clinical professor of medicine at the Yale School of Medicine. “Patients with IBS are going to show up in a provider's office with their current 

. Patients with ulcerative colitis and Crohn's disease are also going to show up in providers offices' with 

 so how does this work in a real world type scenario? And across those 697 patients, they found an efficacy of 73.8% further validating the randomized control trial from phase 3. And of those 73.8%, 91% remained responsive at 6 months. So in a real world, formalized study setting, we see very, very encouraging data.”

Feuerstadt also says in his conversations with patients he explains the differences from taking antibiotics and getting this treatment. 

“If we explain it appropriately, the patients will understand that the antibiotic controls the phase that causes symptoms, but that spore phase, the phase that remains in their system after the antibiotics that requires a healthy, diverse microbiota, and that regrowth of the microbiota without supplementation causes a recurrence. Therefore, if you're putting the microorganisms into the place where the infection is, you're preventing that recurrence. So patients can wrap their head around that concept and understand how you're treating the entire infection and how you're shutting down that cycle of recurrence. And that clicks in their head, where they have that aha moment,” Feuerstadt said.

For those not familiar with Rebyota, it is a live biotherapeutic product (LBP) that is a pre-packaged, single-dose 150 mL microbiota suspension for rectal administration consisting of a liquid mix of up to trillions of live microbes, including 

. Rebyota is delivered directly to the gut microbiome and is administered by a healthcare professional in 1 visit.

. Real-World Effectiveness of Fecal Microbiota, live-jslm for the Prevention of Recurrent Clostridioides difficile Infection. Poster #220 presented at IDWeek 2024. October 16-19, 2024. Los Angeles, CA.



Paul Feuerstadt, MD, FACG, AGAF, discusses what the data says as well as offers insights about what patients can expect and medical peer-to-peer information about the procedure. 

Two Years After its FDA Approval, Rebyota Continues to Show Efficacy and Safety

Arbutus CEO Michael McElhaugh discussed trial results showing that a combination of imdusiran, an RNAi therapeutic, and pegylated interferon alfa-2α can achieve a functional cure in chronic hepatitis B patients.

Imdusiran for Chronic Hepatitis B Achieves Functional Cure in 50% of Patients

Arbutus Biopharma Corporation has announced breakthrough data from its IM-PROVE I Phase 2a clinical trial, demonstrating that a combination of imdusiran (AB-729), an RNA interference (RNAi) therapeutic, and a short course of pegylated interferon alfa-2α (IFN) can achieve a functional cure in patients with chronic hepatitis B virus (cHBV) infection. The data, showing up to 50% of patients achieving a functional cure, will be presented at The Liver Meeting® 2024, hosted by the American Association for the Study of Liver Diseases (AASLD) on November 18.

In our interview with Michael J McElhaugh, interim president and CEO and director of Arbutus Biopharma, he discussed the promising results from the IM-PROVE I trial. “The data from this study reveal significant long-term potential for imdusiran in combination with interferon as a pathway toward a functional cure for cHBV,” McElhaugh said. “This combination has the potential to change the treatment landscape for Hepatitis B.”

The IM-PROVE I trial included HBeAg-negative patients with suppressed HBV who received six doses of imdusiran alongside 24 weeks of interferon, in addition to ongoing nucleos(t)ide analogue (NA) therapy. Results revealed that 50% (3/6) of patients with baseline hepatitis B surface antigen (HBsAg) levels less than 1000 IU/mL achieved a functional cure, defined as sustained HBsAg loss and undetectable HBV DNA for 24 weeks after stopping all treatments. Overall, 25% (3/12) of patients across the cohort achieved a functional cure.

According to McElhaugh, the IM-PROVE I study focused on evaluating the combination of imdusiran and interferon in e-antigen-negative patients who had previously been chronically suppressed with nucleoside analogs, the current standard of care. The trial tested four different treatment regimens to evaluate how well imdusiran could reduce surface antigen levels, a key marker of the virus, in combination with interferon over periods ranging from 12 to 24 weeks.

“The primary goal of this trial was to reduce surface antigen levels with imdusiran,” McElhaugh explained. “After the interferon phase, we paused all treatments and monitored patients for 24 weeks without therapy, which is the regulatory definition of a functional cure. This means Hepatitis B DNA is undetectable, and surface antigen is lost or reduced to below the limit of quantification.”

The results from the study were groundbreaking, particularly in the group that received imdusiran continuously in combination with 24 weeks of interferon. In this cohort, 25% of patients achieved a functional cure, a result McElhaugh calls “one of the best seen in the field.” Even more notable was the response rate in patients with baseline surface antigen levels below 1,000 IU/mL, where 50% of patients achieved a functional cure.

“This patient population is key,” McElhaugh emphasized. “Hepatitis B is a major global health issue, but even focusing on a subset—such as those with lower baseline surface antigen levels—can make a big difference. Achieving a functional cure in half of these patients is a very promising result.”

When asked about factors that influenced which patients were more likely to achieve a functional cure, McElhaugh highlighted baseline surface antigen levels as the most significant predictor. Patients with surface antigen levels below 1000 IU/mL had a markedly higher chance of success compared to those with higher levels.

“We saw that patients with lower surface antigen levels were more likely to achieve a functional cure,” McElhaugh noted. “That’s a critical insight for optimizing treatment regimens moving forward.”

Comparing imdusiran to other RNAi therapies in development for Hepatitis B, McElhaugh shared that Arbutus' product stands out due to its ability to induce immune activation. Unlike other siRNA treatments, which have largely been considered similar in their mechanisms, imdusiran has demonstrated the capacity to prime the immune system and activate T-cells during the initial treatment phase.

“This immune activation makes imdusiran different from other siRNAs,” McElhaugh explained. “It creates a better environment for immune-modulatory treatments like interferon to work more effectively. These differences, such as the structure and delivery mechanisms of the siRNA, contribute to the better outcomes we’re seeing.”

Looking ahead, McElhaugh revealed that Arbutus is eager to move imdusiran into later-stage development as quickly as possible. The company is currently in discussions about the best path forward, including engagement with regulatory agencies to ensure the swift progression of the therapy. “Our goal is to maximize the functional cure rates we’ve seen with imdusiran and bring it to patients as soon as we can,” McElhaugh said.

Although the AASLD conference had just kicked off, McElhaugh expressed optimism about the reception of the data so far. “We’ve had a packed schedule of meetings, and everyone we've spoken to has been very impressed with the results,” he shared. “It’s been a rough day in the markets, but we’re feeling confident about where we stand with imdusiran.”

Press Release. Arbutus’ Imdusiran Achieves Functional Cure in cHBV Patients when Combined with a Short Course of Interferon. Arbutus Biopharma. November 15, 2024. Accessed November 18, 2024. 

https://investor.arbutusbio.com/news-releases/news-release-details/arbutus-imdusiran-achieves-functional-cure-chbv-patients-when

Conferences

Bruce Jones, PharmD, FIDSA, BCPS provided insights on challenging patients with comorbidities such as type 2 diabetes and higher BMI.

Challenges of Treating Patients With Staphylococcus aureus

What is the clinical challenges of treating 

 When considering serious infections, particularly those like bacteremia, patient outcomes can be severe. Bacteremia, for example, comes with a high mortality rate—often 25-30%, with some studies reporting even higher rates. Complications, such as dissemination or endovascular involvement, are common in these patients, and resistance profiles, such as MRSA versus MSSA, play a critical role.

For our institution, 2023 marked one of the first years we saw MRSA rates dip below 50%, while previous years have been higher. The national average tends to run around 42-45%. Dealing with MRSA presents challenges, as it limits our treatment options, increases healthcare costs, and extends hospital stays, making it difficult to manage these patients effectively. Interestingly, some of the most severe cases of bacteremia I've encountered have been MSSA bacteremias, but MRSA still complicates treatment due to its resistance profile.

We've made efforts to improve outcomes in bacteremia cases through standardized protocols, including pathways, bundling, and more consistent care practices. For instance, MRSA or any staphylococcus aureus bacteremia now requires an infectious disease (ID) consult to ensure optimal management. This includes ensuring an echocardiogram is performed, blood cultures are repeated, and overall treatment is optimized to manage these serious infections appropriately.

What are some of the difficulties in treating complicated patients with comorbidities, such as obesity, type 2 diabetes, you need to factor in during treatment?

 We always aim to include patients with real-world characteristics in phase three trials, right? Because we want to ensure these trials reflect the types of patients we see daily. From a pharmacist's perspective, comorbidities are a frequent consideration. When I see comorbidities, I immediately think about the treatments they’ll need, which often leads to concerns about drug-drug interactions, drug-disease interactions, side effects, and adverse events—factors that all require careful management and additional thought.

Looking at the big picture, these patients, depending on the type of infection, are known for having higher 30-day readmission rates. They also have a greater likelihood of harboring resistant organisms due to frequent healthcare exposure, which increases the risk of 

and other complications that demand extra attention and management.

The conversation was edited for grammar and clarity.

COVID-19 and Immunocompromised Individuals


On May 5, 2023, the World Health Organization declared an end to the global health emergency phase of COVID-19, the disease caused by the novel coronavirus SARS-CoV-2.

The virus is estimated to have infected more than 775 million individuals worldwide and is attributed to more than 7 million deaths.

 The landscape of COVID-19 has shifted throughout the years with the development and identification of pharmacologic agents used for prevention and treatment, as well as with the evolution of new SARS-CoV-2 variants.

The development of effective COVID-19 vaccines was paramount to the pandemic response, protecting against severe disease while helping to reduce new outbreaks of the virus.

 However, patients with compromised immune systems may be unable to receive adequate protection from the latest vaccinations and remain at risk of severe disease, owing to suboptimal antibody response and inadequate levels of SARS-CoV-2 neutralizing antibodies following vaccination.

This is best illustrated by results of an observational study to assess COVID-19 health outcomes of immunocompromised individuals compared with the general population in the United Kingdom using data from the National Health Service during 2022.

 Of nearly 12 million patients, only 3.9% were classified as immunocompromised, yet this cohort made up 22% of COVID-19 hospitalizations, 28% of COVID-19 intensive care unit admissions, and 24% of COVID-19 related deaths. Patients with more profound immunosuppressive conditions (eg, stem cell transplant within 2 years or solid organ transplant) were at the highest risk for adverse COVID-19 outcomes.

Seropositivity Following COVID-19 Vaccination in Immunocompromised Individuals


Several vaccine response studies have found decreased seropositivity in immunocompromised individuals compared with those without immune compromise. Haider et al conducted a prospective observational study to measure antibody responses and neutralization titers following COVID-19 vaccination in individuals with a range of immunocompromising conditions compared with immunocompetent health care workers (HCWs).

 The study enrolled 1271 participants (1099 immunocompromised and 172 immunocompetent HWCs) from April to July 2021. Seropositivity was lower among those with solid organ transplants (30.7%), hematological malignancies (50.0%), autoimmune conditions (79.1%), solid tumors (78.7%), and HIV (79.8%) compared with immunocompetent HCWs (92.4%) (

< .01 for all). Neutralization titers were also significantly lower in immunocompromised individuals compared with immunocompetent HCWs. Additionally, in a systematic review and meta-analysis, Lee et al compared rates of seroconversion in immunocompromised individuals with those without immune compromise following the first and second doses of the COVID-19 vaccine.

 Seroconversion rates following both COVID-19 vaccine doses were significantly lower in organ transplant recipients and those with solid cancers, hematological cancers, and immune-mediated inflammatory disorders than the immunocompetent controls. Based on decreased rates of seropositivity following COVID-19 vaccination, it has been theorized that certain immunocompromised individuals may benefit from passive immunity through preventive monoclonal antibody infusions.

Monoclonal antibodies are synthetic proteins that mimic the immune system’s ability to fight off pathogens such as the SARS-CoV-2 virus. Anti–SARS-CoV-2 monoclonal antibodies have been utilized as prophylactic agents for COVID-19 in individuals with moderate to severe immune compromise.

Tixagevimab/cilgavimab (Evusheld) was the first monoclonal antibody authorized by the US Food and Drug Administration (FDA) for pre-exposure prophylaxis (PrEP) against SARS-CoV-2. Unfortunately, new SARS-CoV-2 variants emerged with reduced neutralizing susceptibility to tixagevimab/ cilgavimab, which led to the withdrawal of the Emergency Use Authorization (EUA) for tixagevimab/cilgavimab.

In March 2024, the FDA issued an EUA for pemivibart (Pemgarda) for use as PrEP against SARS-CoV-2 in individuals 12 years or older with moderate to severe immune compromise (

Pemivibart is a recombinant human monoclonal antibody that targets the spike protein receptor binding domain of SARS-CoV-2, thus preventing the virus from attaching to host cells. The FDA’s authorization came after the release of data establishing immunobridging for pemivibart, a study end point often used in monoclonal antibody clinical trials. Immunobridging for pemivibart was established by comparing serum antibody titer response at day 28 for variant JN.1 (the predominant variant in circulation at the time) with historical antibody titer data of adintrevimab against the Delta variant. It was determined that serum-neutralizing titers of pemivibart for JN.1 were consistent with those of previously authorized monoclonal antibodies against COVID-19.

In clinical studies, pemivibart was administered as a single 4500-mg intravenous infusion over at least 60 minutes.

 Repeat dosing every 3 months may be performed to ensure serum antibody titers persist at adequate levels. For patients who have been recently vaccinated against COVID-19, pemivibart should be administered at least 2 weeks after vaccination. Like previously authorized monoclonal antibodies for COVID-19, the medication should be administered only in settings where health care providers are accessible and able to treat adverse reactions, including anaphylaxis. It is recommended to monitor patients during and for at least 2 hours following completion of the infusion. In clinical studies, the most commonly reported adverse reactions included upper respiratory tract infection (6%), local infusion site reactions (5%), and systemic infusion-related and hypersensitivity reactions (4%); there were rare reports of anaphylaxis (0.6%).

As mentioned previously, JN.1 was the pre-dominant sublineage at the time of pemivibart’s authorization for use as COVID-19 PrEP. Since then, there has been a continual change in predominant COVID-19 variants and sublineages. The most recent data from the Centers for Disease Control and Prevent-ion’s national SARS-CoV-2 genomic surveil-lance system for the 2 weeks ending August 31, 2024, show predominant circulating JN.1 sublineages to be KP.3.1.1 (42.2%), KP.2.3 (16.4%), KP.3 (14.2%), and LB.1 (13.5%).10 Of note, sublineage KP.3.1.1 continues to spread and is now the predominant SARS-CoV-2 variant circulating in the US.

In recent weeks, at least 2 non–peer-reviewed studies assessing pemivibart’s in vitro neutralizing activity against the current circulating JN.1 sublineages, including JN.1.1, LB.1, KP.2.3, KP.3, KP.3.3, and KP.3.1.1 have been posted online.

 The results of these studies have raised questions regarding the effectiveness of pemivibart against select sublineages, most notably KP3.1.1. However, in response to the newly circulating variants, on September 3, 2024, Invivyd, Inc, issued a news release announcing its reference laboratory had confirmed continued neutralizing activity of pemivibart against LB.1 and KP.3.1.1.13 Details on pemivibart’s neutralization activity and 50% effective concentration (EC50) against KP3.1.1, LB.1, and other variants of interest have not yet been released but are likely to appear in an upcoming update to the medication’s prescribing information.

The news release suggested that pemivibart has maintained the ability to produce sufficient virus-neutralizing antibody titers against current circulating variants and remains an option for PrEP for those with moderate to severe immune compromise.

In August 2024, the Infectious Diseases Society of America published a clinical practice guideline update on the use of pemivibart as PrEP for COVID-19.

 The focused update suggests using pemivibart for PrEP in patients with moderate or severe immune compromise when predominant regional variants are susceptible (conditional recommendation with low certainty of evidence). The current EUA authorizes use of pemivibart for PrEP for as long as the combined national frequency of COVID-19 variants with substantially reduced susceptibility is 90% or less. With the recent statement from Invivyd, which suggested pemivibart maintained antibody neutralization activity against the current US predominant variant KP3.1.1, use of pemivibart for patients with moderate to severe immune compromise appears to be a practical option for patients unlikely to achieve protection from COVID-19 vaccines. Ongoing evaluation of pemivibart and its ability to produce sufficient neutralizing antibody titers against future COVID-19 variants will be needed.

Although vaccination remains the first-line prevention against COVID-19, some individuals with profound immunosuppression may not mount an adequate response to vaccination. Anti–SARS-CoV-2 monoclonal antibodies have been developed as prophylactic agents for COVID-19 in individuals with moderate to severe immune compromise. Currently, pemivibart is the only monoclonal antibody agent authorized for PrEP of COVID-19. As new SARS-CoV-2 variants continue to emerge, it is essential to evaluate pemivibart’s effectiveness against new variants.

Sarker R, Roknuzzaman ASM, Nazmunnahar, Shahriar M, Hossain J, Islam R. The WHO has declared the end of pandemic phase of COVID-19: way to come back in the normal life. 

New therapeutics offer some hope in this emerging market.

Ammara Mushtaq, MD

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